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In this article, a nonlinear control method based on a virtual synchronous inverter is presented in order to maintain the stability of the microgrid in the island and connected mode with the presence of solar renewable energy sources. Uncertainty about solar renewable energy sources is modeled using the distribution function. Also, in order to optimize the parameters of the nonlinear control method, a sailfish optimization algorithm has been used. The proposed method is implemented on a microgrid with three distributed generation sources. The obtained results show the effectiveness of the proposed method in damping power and voltage fluctuations in both islanded and grid-connected modes, as well as when changing the working mode of the microgrid.

Ethyl methanesulfonate (EMS)-induced mutagenesis is a prominent method for generating plant mutants, often resulting in chimera plants; however, their transcriptional and genetic characteristic remain elusive. In this investigation, chimera pea (Pisum sativum L.) specimens, labeled GY1 and GY2, exhibiting a distinctive phenotype with yellow and green leaves were meticulously cultivated via sequential double EMS mutagenesis. The observed color disparity between the yellow and green leaves was attributed to a significant reduction in chlorophyll content coupled with heightened lutein levels in both chimeric variants. Transcriptome profiling revealed the enrichment of differentially expressed genes in both GY1 and GY2, specifically implicating Kyoto Encyclopedia of Genes and Genomes pathways linked to amino acid biosynthesis and ribosome development, alongside Gene Ontology (GO) biological processes linked with stress response mechanisms. Few structural genes associated with chlorophyll and lutein biosynthesis exhibited discernible differential expression. Despite these functional similarities, distinctive nuances were evident between specimens, with GY1 exhibiting enrichment in GO pathways related to chloroplast development and GY2 showing enrichment for ribosome development pathways. Single-nucleotide polymorphism (SNP) analysis uncovered a shared pool of 599 and 598 polymorphisms in the yellow and green leaves of GY1 and GY2, respectively, likely stemming from the initial EMS mutagenesis step. Further investigation revealed an increased number of unique SNPs in the yellow leaves following the second EMS application, whereas the green leaves exhibited sparse and unique SNP occurrences, suggestive of potential evasion from secondary mutagenesis. This inherent genetic variability underpins the mechanism underlying the formation of chimera plants. Predominant base mutations induced by EMS were characterized by G/A and C/T transitions, constituting 74.1% of the total mutations, aligning with established EMS mutation induction paradigms. Notably, genes encoding the eukaryotic translation initiation factor eIIso4G and the ubiquitin ligase RKP, known to modulate leaf color in model plants, harbored two SNPs in the yellow leaves of both GY1 and GY2, implicating their putative role in the yellow leaf phenotype. Collectively, this study provides novel insights into the transcriptional and genetic characteristics of chimera plants via EMS-induced mutagenesis.

Abstract This study aimed to explore the changes of pharmacokinetic parameters after meropenem in patients with abdominal septic shock after gastrointestinal perforation, and to simulate the probability of different dosing regimens achieving different pharmacodynamic goals. The study included 12 patients, and utilized high performance liquid chromatography-tandem mass spectrometry to monitor the plasma concentration of meropenem. The probability of target attainment (PTA) for different minimum inhibitory concentration (MIC) values and %fT > 4MIC was compared among simulated dosing regimens. The results showed that in 96 blood samples from 12 patients, the clearance (CL) of meropenem in the normal and abnormal creatinine clearance subgroups were 7.7 ± 1.8 and 4.4 ± 1.1 L/h, respectively, and the apparent volume of distribution (Vd) was 22.6 ± 5.1 and 17.2 ± 5.8 L, respectively. 2. Regardless of the subgroup, 0.5 g/q6h infusion over 6 h regimen achieved a PTA > 90% when MIC ≤ 0.5 mg/L. 1.0 g/q6h infusion regimen compared with other regimen, in most cases, the probability of making PTA > 90% is higher. For patients at low MIC, 0.5 g/q6h infusion over 6 h may be preferable. For patients at high MIC, a dose regimen of 1.0 g/q6 h infusion over 6 h may be preferable. Further research is needed to confirm this exploratory result.

Abstract Objective There is a lack of standard salvage treatment options for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) that has failed platinum-containing regimens. Breakthroughs in immunotherapy have opened up new options for these patients. However, the efficacy and safety of immunotherapy have not been clarified. This study aimed to summarize and assess the efficacy and safety of PD-1 inhibitors in patients with RM-NPC who failed platinum-containing chemotherapy. Methods Up to August 25, 2022, clinical trials of PD-1 inhibitors in RM-NPC patients who failed platinum-containing regimens were searched in the PubMed, Embase, Cochrane, and Web of Science databases. Retrieval subject terms included “nasopharyngeal carcinoma”, “metastatic”, “recurrence”, “PD-1”, and “PD-L1”. The clinical trials eligible for inclusion were systematically reviewed and meta-analyzed. Results A total of 9 studies including 842 patients with RM-NPC were included in this meta-analysis. The results showed that PD-1 inhibitors had promising efficacy in patients with RM-NPC who failed platinum-containing regimens: objective response rate (ORR) was 24% (95% confidence interval [CI] 21–26%), disease control rate (DCR) was 52% (95% CI 45–58%), 1-year progression-free survival (PFS) rate was 25% (95% CI 18–32%), and 1-year overall survival (OS) rate was 53% (95% CI 37–68%). In terms of treatment-related adverse events (AEs), the incidence of grade ≥ 3 treatment-related AEs was 19% (95% CI 13–24%). In addition, we found that PD-1 inhibitors were more effective in patients with PD-L1 positive than in patients with PD-L1 negative nasopharyngeal carcinoma who had failed platinum-containing regimens (ORR 31% (95%CI 26–35%) vs. 21% (95% CI 17–25%)). Conclusion PD-1 inhibitors may provide a survival benefit for patients with RM-NPC who have failed platinum-containing regimens and have the advantage of a good safety profile, making them a promising treatment option.

Abstract BeiDou Satellite-based Augmentation System (BDSBAS) has come into the trial operation stage since July, 2020. To evaluate the characteristic of the augmentation message in BDSBAS-B1C signal, the effectiveness of the message content was firstly analyzed, and then the validity of the broadcasting strategy was estimated. Finally, the accuracy of the user equivalent ranging error (UERE) and the single frequency positioning error with different correction parameters in BDSBAS-B1C message was evaluated. Based on the above analysis, the effectiveness of the augmentation message was preliminarily verified with the results showing that: (1) the BDSBAS-B1C message type, information content and update interval have basically met the international standard; (2) the accuracy of the UERE obtained with the augmentation message had an obvious improvement in contrast to that of the UERE obtained with the usual navigation message of the GPS satellites, and the ionospheric delay was one of the important factors which affected the accuracy of the UERE; (3) the positioning accuracy obtained with the augmentation message was also improved, and the improvement was more obvious in the service areas with high availability of the ionospheric parameters.

Abstract This study aimed to investigate Hippo pathway-related prognostic long noncoding RNAs (lncRNAs) and their prognostic value in liver hepatocellular carcinoma (LIHC). Expression and clinical data regarding LIHC were acquired from The Cancer Genome Atlas and European Bioinformatics Institute array databases. Hippo pathway-related lncRNAs and their prognostic value were revealed, followed by molecular subtype investigations. Differences in survival, clinical characteristics, immune cell infiltration, and checkpoint expression between the subtypes were explored. LASSO regression was used to determine the most valuable prognostic lncRNAs, followed by the establishment of a prognostic model. Survival and differential expression analyses were conducted between two groups (high- and low-risk). A total of 313 Hippo pathway-related lncRNAs were identified from LIHC, of which 88 were associated with prognosis, and two molecular subtypes were identified based on their expression patterns. These two subtypes showed significant differences in overall survival, pathological stage and grade, vascular invasion, infiltration abundance of seven immune cells, and expression of several checkpoints, such as CTLA-4 and PD-1/L1 (P

This prospective study investigated the relationship between the lipoprotein-associated phospholipase A2 (Lp-PLA2) level and cognitive impairment (CI) in type II diabetes mellitus (TIIDM) patients with white matter hyperintensity (WMH). A total of 87 TIIDM patients diagnosed with WMH were included in this study. They were grouped into CI group and noncognitive impairment (NCI) group based on the MoCA scales. The serum Lp⁃PLA2 levels and MoCA scores of the patients with WMH were compared with those of control (Ctl). Logistic regression was used to analyze the risk factors affecting CI and diagnostic value of serum Lp⁃PLA2 for CI. The WMH group had significantly higher serum level of Lp⁃PLA2 and significantly lower MoCA score than Ctl group. There were significant differences in serum levels of homocysteine, high-density lipoprotein cholesterol (HDL-C) and Lp⁃PLA2 (P

Diabetic vascular complications can affect both microvascular and macrovascular. Diabetic microvascular complications, such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and diabetic cardiomyopathy, are believed to be caused by oxidative stress. The Nox family of NADPH oxidases is a significant source of reactive oxygen species and plays a crucial role in regulating redox signaling, particularly in response to high glucose and diabetes mellitus. This review aims to provide an overview of the current knowledge about the role of Nox4 and its regulatory mechanisms in diabetic microangiopathies. Especially, the latest novel advances in the upregulation of Nox4 that aggravate various cell types within diabetic kidney disease will be highlighted. Interestingly, this review also presents the mechanisms by which Nox4 regulates diabetic microangiopathy from novel perspectives such as epigenetics. Besides, we emphasize Nox4 as a therapeutic target for treating microvascular complications of diabetes and summarize drugs, inhibitors, and dietary components targeting Nox4 as important therapeutic measures in preventing and treating diabetic microangiopathy. Additionally, this review also sums up the evidence related to Nox4 and diabetic macroangiopathy.

A type of manipulator configuration with four-fingers is put forward, for grasping fragile hollow workpieces, with adjustable finger length and finger pad shape. Within a certain range, the manipulator can be used to grasp the internal cross section of fragile objects with different size of circular and oval shape. The design idea and structure of the manipulator are introduced, while the join positions between the finger pad and the finger body, as determined by uniform interpolation or Chebyshev interpolation, are comparatively analyzed and researched regarding forming force contact with workpiece. During the process of grasping, the internal forces and deformations between finger pad and workpiece are analyzed, based on a constructed finite element analysis model. The calculation example shows that, under the same grasping parameters, the maximum impact force on the workpiece is reduced by 63%, when the curvature adjustment points for the finger pad are distributed according to the Chebyshev interpolation, compared to their equal spacing distribution. Research has provided a theoretical basis for the design optimization of the finger pad structure and the connection point positions. For using manipulator to grasp objects with different size of circular and oval shape, the working space of the proposed manipulator is studied. The experiments show that, the manipulator structure, as presented in this article, can meet the requirements of relevant tasks.

Abstract N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins.

IntroductionTrace element metabolism disorders are often secondary to disorders of glucose metabolism in diabetes. Although 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] could ameliorate abnormal glucose metabolism in the development of diabetes, the effect on trace element metabolism is unclear. The objective of this study was to evaluate the influence of 1,25(OH)2D3 on urinary excretions of trace elements in Zucker diabetic fatty (ZDF) rats.MethodsAt 6 weeks of age, male ZDF (n = 40) rats were subdivided into four groups: diabetic model (ZDF), low-dose (ZDF + VL, 2 μg/kg⋅bw), middle-dose (ZDF + VM, 8 μg/kg⋅bw) and high-dose (ZDF + VH, 16 μg/kg⋅bw) 1,25(OH)2D3 groups. Another 10 Zucker lean (ZL) rats served as a control group. All rats were given vitamin D deficient Purina #5008 chow and the intervention groups were given the corresponding dose of 1,25(OH)2D3 by gavage on alternate days for 7 weeks. Microalbuminuria (MALB) and urinary creatinine concentration were detected by a biochemical autoanalyzer. Urine trace element concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) and were corrected by urinary creatinine.ResultsThroughout the intervention phase, MALB, UACR and urinary creatinine levels in the ZDF group were significantly higher than those in the ZL group, and showed a gradual increase with the prolongation of the intervention time. These changes were reversed in a dose-dependent manner after 1,25(OH)2D3 intervention (P < 0.05). Correspondingly, most of the urinary trace element excretions in the ZDF rats were significantly increased compared with the ZL group, and 1,25(OH)2D3 intervention significantly reduced the urinary copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo) levels in the ZDF rats (P < 0.05), especially in the medium and high dose groups.Conclusion1,25(OH)2D3 had improvement effects on urinary Cu, Zn, Se, and Mo excretions in ZDF rats, suggesting that it may be related to the reduction of diabetic renal impairment and renal oxidative damage.

The awnless trait is the favorite trait for wheat breeding in Qinghai, China, but the major gene underlying the trait is unknown. This study aimed to analyze a recombinant inbred line (RIL) population containing 112 lines by crossing common wheat varieties GY448 (awnless) and GY115 (awned) using genotyping-by-sequencing analysis. A total of 56.62 Gb of clean sequence data were generated. A major gene was identified for the awnless trait based on 101,275 single-nucleotide polymorphisms by quantitative trait locus (QTL)-seq analysis. The region from 685.50 to 709.77 Mb on chromosome 5AL contained 334 genes and 394 transcripts, including B1, the major gene controlling the awnless trait. A 25-bp indel located in the B1 promoter region has a diagnostic value for the awnless/awned genotypes in the RIL population. A total of 42 spring wheat cultivars in Qinghai, China, were analyzed. Further, 23 awnless cultivars had the alleles of the GY448 parent, while 19 awned cultivars had the alleles of the GY115 parent. B1 is crucial in the awnless trait in wheat cultivars in Qinghai, China. The findings of this study might guide the breeding of new wheat cultivars in this region.

Red-fleshed pummelo (Citrus grandis), a mutant of ‘Guanxi’, is an important economic plant rich in carotenoids. The transcriptome of ‘Guanxi’ pummelo was compared with red-fleshed pummelo, with the aim of identifying the key genes responsible for red flesh through RNA sequencing. In total, 44.11 and 47.71 Gb clean reads were respectively obtained after filtering in red and white flesh. Altogether 46,425 unigenes, with an average length of 1208 bp, were assembled. Compared with that of white flesh, 3722 genes were up-regulated, whereas 1421 genes appeared down-regulated in the red-fleshed pummelo. A GO analysis assigned 11,983 differentially expressed genes to 53 subcategories, and 3582, 4722 and 3679 differentially expressed genes were involved in biological processes, cellular components and molecular functions, respectively. The mevalonate pathway involved in terpenoid backbone biosynthesis was significantly different between ‘Guanxi’ pummelo and its red-fleshed mutant, and the differences were closely associated with carotenoid biosynthesis. The expression levels of the carotenoid biosynthetic pathway genes were different between ‘Guanxi’ pummelo and its red-fleshed mutant, with the upstream genes having higher expression levels in red-fleshed pummelo than in ‘Guanxi’ pummelo, whereas the downstream gene β-CHX was downregulated. Two bHLH transcription factors (CL4778.Contig1 and CL4778.Contig2) were of the same branch as CubHLH1, regulating carotenoid biosynthesis in Citrus unshiu Marc., and Unigene CL4778.Contig2 had expression differences in two kinds of pummelo, which suggested CL4778.Contig2 should be a candidate gene controlling carotenoid accumulation in red pummelo. The study would be beneficial to identify the major gene regulating the red flesh trait.

Quinoa (Chenopodium quinoa Willd.) cultivars that produce black grains are thought to be more nutritious and contain powerful antioxidant properties, but little is known about the chemical foundation and the genetic mechanism behind this trait. In this research, widely-targeted metabolome and transcriptome analyses were employed to unveil the chemical and genetic differences between black and white quinoa cultivars. A total of 157 differentially expressed metabolites were found in the black and white quinoa cultivars. The tannins and flavonoids were present at high levels in the black quinoa grains. The tannins comprised 13 proanthocyanins, all of which could barely be detected in white grains. Proanthocyanidins are suggested to cause the black grain trait in Arabidopsis thaliana and Brassica species and are thought to produce the black grain trait, while contributing to antioxidant activity, in black grain quinoa. A total of 4620 differentially expressed unigenes were identified in the black and white quinoa grains. Structural genes associated with proanthocyanin biosynthesis, particularly DFR, LAR, LDOX and ANR, were more highly expressed in black than white grains. Genes involved in the betalain biosynthetic pathway, which competes with anthocyanin biosynthesis, showed relatively lower levels of expression in black grains. Two MYB and one MYC transcription factor related to the phenylpropane metabolic pathway displayed higher expression levels in black grains, while BvMYB1, associated with betalain biosynthesis, was not detected. This study suggested that the accumulation of proanthocyanins produces the black grain trait in quinoa, and the activation of transcription factors triggers the proanthocyanidin biosynthesis pathway.

3D printed titanium implants have gained substantial attention in the medical fields of bone tissue and dental implants. Surface modification of titanium implants such as TiO2 nanotubes (TNT) make up for the interaction between the surface of titanium implants and the surrounding tissues by providing nanoporous structures and hydrophilic surfaces. In this study, a 3D printed Cu-bearing Ti6Al4V (TC4) alloy with micro/nano-topographical was employed as material model to explore the role played by Cu2+ and nanostructure in the physical–chemical properties of the material, osteoblast toxicity. The role of Cu2+ and nanostructure on macrophage proliferation, polarization and oxidative stress without and with lipopolysaccharide (LPS) stimulation was also evaluated. Surface characterizations showed TNT significantly increased the roughness and surface hydrophilicity of TC4 alloy. TNT-TC4-5Cu exhibited excellent corrosion properties in the absence and presence of LPS. The in vitro tests with MC3T3-E1 cells demonstrated that the TNT-TC4-5Cu alloys showed the better cytocompatibility. Moreover, TNT-TC4-5Cu alloy can inhibit macrophage polarization and decreased ROS generation without and with LPS stimulation, thereby promoting the biocompatibility. In summary, the TNT-TC4-5Cu alloy promoted the proliferation and adhesion of osteoblasts and inhibited the inflammatory response of macrophages, which has great potential to benefit the future development of orthopedic applications.

The inter-satellite link is an important technology to improve the accuracy of clock offset measurement and prediction for BeiDou Navigation Satellite System (BDS). At present, BDS measures clock offsets of invisible satellite mainly through the “one-hop” reduction mode based on the satellite-ground clock offset of the node visible satellite and the inter-satellite clock offset between the two satellites. However, there exists a systematic deviation caused by the node satellite reduction, and there is still a large room for improvement in clock offset measurement and prediction. Therefore, this paper firstly proposes a method of whole-network adjustment for clock offset based on the satellite-ground and inter-satellite two-way data. The least square method is used to realize the whole-network adjustment of clock offset based on the observations of two sources, and to obtain optimal estimates of different clock offset reduction. Secondly, the evaluation method combining internal and external symbols are proposed by the fitting residual, prediction error and clock offset closure error. Finally, experimental verification is completed based on BDS measured data. In comparison with the “one-hop” reduction method, the fitting residual and prediction error of the whole-network adjustment method reduces about 45.06% and 52.15%, respectively. In addition, inter-satellite station closure error and three-satellite closure error are reduced from 0.69 ns and 0.23 ns to about 0 ns. It can be seen that the accuracy of BDS time synchronization is significantly improved.

Hyperuricemia-induced cardiac remodeling is at least in part via pressure-dependent mechanisms, yet the pressure-independent mechanisms are not well understood. C-X-C motif chemokine ligand 1 (CXCL1) was upregulated in renal tubules from mice subjected to uric acid (UA)-induced nephropathy. Given that CXCL1 is a master chemokine responsible for the recruitment of macrophage by binding with its receptor C-X-C motif chemokine receptor 2 (CXCR2), we thus hypothesized that UA-induced cardiac injury is via promoting the recruitment of CXCR2 + macrophages into the heart, which enhances cardiac inflammation. Within a mouse model of UA injection (500 mg/kg, twice/day, 14 days), we measured the level of cardiac CXCL1. We also tested the efficacy of the CXCR2 antagonist on UA-induced cardiac inflammation and remodeling. We found a high plasma level of UA-induced upregulation of CXCL1 in heart tissues. CXCR2 antagonist relieved UA-induced cardiac hypertrophy and suppressed cardiac inflammation and fibrosis. The silencing of CXCR2 in human monocytes abolished the migration of UA-induced monocyte. Thus, the interventions against CXCL1/CXCR2 may be effective for the prevention and treatment of UA-induced cardiac hypertrophy and inflammatory responses.

Abstract Introduction Targeted therapies are based on specific gene alterations. Various specimen types have been used to determine gene alterations, however, no systemic comparisons have yet been made. Herein, we assessed alterations in selected cancer‐associated genes across varying sample sites in lung cancer patients. Materials and Methods Targeted deep sequencing for 48 tumor‐related genes was applied to 153 samples from 55 lung cancer patients obtained from six sources: Formalin‐fixed paraffin‐embedded (FFPE) tumor tissues, pleural effusion supernatant (PES) and pleural effusion cell sediments (PEC), white blood cells (WBCs), oral epithelial cells (OECs), and plasma. Results Mutations were detected in 96% (53/55) of the patients and in 83% (40/48) of the selected genes. Each sample type exhibited a characteristic mutational pattern. As anticipated, TP53 was the most affected sequence (54.5% patients), however this was followed by NOTCH1 (36%, across all sample types). EGFR was altered in patient samples at a frequency of 32.7% and KRAS 10.9%. This high EGFR/ low KRAS frequency is in accordance with other TCGA cohorts of Asian origin but differs from the Caucasian population where KRAS is the more dominant mutation. Additionally, 66% (31/47) of PEC samples had copy number variants (CNVs) in at least one gene. Unlike the concurrent loss and gain in most genes, herein NOTCH1 loss was identified in 21% patients, with no gain observed. Based on the relative prevalence of mutations and CNVs, we divided lung cancer patients into SNV‐dominated, CNV‐dominated, and codominated groups. Conclusions Our results confirm previous reports that EGFR mutations are more prevalent than KRAS in Chinese lung cancer patients. NOTCH1 gene alterations are more common than previously reported and reveals a role of NOTCH1 modifications in tumor metastasis. Furthermore, genetic material from malignant pleural effusion cell sediments may be a noninvasive manner to identify CNV and participate in treatment decisions.

To improve the absolute positional accuracy of the serial six-DOF robot， the joint stiffness error of industrial robots after geometric parameter error compensation is studied. Firstly，the one-dimensional joint stiffness error model of industrial robots is established based on the virtual joint model. Secondly，in order to improve the identification accuracy and efficiency of joint stiffness parameters, the BP neural network is applied to fit the stiffness error model to optimize the initial population fitness of genetic algorithm. Finally，the laser tracker AT930 and ER10L-C10 robot are used to verify the above error model and joint stiffness parameter identification algorithm. The experimental results show that the average distance error and maximum distance error of the robot are 0.248 5 mm and 0.333 2 mm respectively after the joint stiffness error compensation. Compared with the distance error before error compensation，the positional accuracy of robot is improved by 33.7%. Therefore，through the proposed improved genetic algorithm can identify the joint stiffness parameters accurately and improve the positional accuracy effectively.

Radio determination satellite service (RDSS) is one of the characteristic services of Beidou navigation satellite system (BDS), and also distinguishes with other GNSS systems. BDS-3 RDSS adopts new signals, which is compatible with BDS-2 RDSS signals in order to guarantee the services of old users. Moreover, the new signals also separate civil signals and military signals which are modulated on different carriers to improve their isolation and RDSS service performance. Timing is an important part of RDSS service, which has been widely used in the field of the power, transportation, marine and others. Therefore, the timing accuracy, availability and continuity is an important guarantee for RDSS service. This paper summarizes the principle of one-way and two-way timing, and provides the evaluation method of RDSS timing accuracy, availability and continuity. Based on BDS-3 RDSS signal measurements of system, the performance of one-way timing and two-way timing is analyzed and evaluated for the first time. The results show that: (1) the accuracy of one-way timing and two-way timing is better than 30 ns and 8 ns respectively, which are better than the official claimed accuracy; (2) the RMS of one-way timing accuracy is 5.45 ns, which is 20% smaller than BDS-2, and the availability and continuity are 100%; (3) the RMS of two-way timing accuracy is 3.59 ns, which is 34% smaller than one-way timing, and both of the availability and continuity are 100%; (4) the orbit maneuver of GEO satellite make the one-way timing has 7.68 h recovery, but has no affection on the two-way timing.

Aldosterone affects myocardial fibrosis and remodeling. The aim was to investigate the relationship between plasma aldosterone concentration (PAC) and left atrial (LA) function in hypertension. 148 hypertensive patients were studied. LA phasic function was evaluated by strain and strain rate imaging. Patients were divided into two groups based on PAC. LA early diastolic strain and strain rate (LAS-E and LASR-E) were lower in group II compared with group I (P ​

Botulinum neurotoxins (BoNTs) cause the disease called botulism, which can be lethal. BoNTs are proteins secreted by some species of clostridia and are known to cause paralysis by interfering with nerve impulse transmission. Although the human lethal dose of BoNT is not accurately known, it is estimated to be between 0.1 μg to 70 μg, so it is important to enable detection of small amounts of these toxins. Our laboratory previously reported on the development of Endopep-MS, a mass-spectrometric‑based endopeptidase method to detect, differentiate, and quantify BoNT immunoaffinity purified from complex matrices. In this work, we describe the application of Endopep-MS for the analysis of thirteen blinded samples supplied as part of the EQuATox proficiency test. This method successfully identified the presence or absence of BoNT in all thirteen samples and was able to successfully differentiate the serotype of BoNT present in the samples, which included matrices such as buffer, milk, meat extract, and serum. Furthermore, the method yielded quantitative results which had z-scores in the range of −3 to +3 for quantification of BoNT/A containing samples. These results indicate that Endopep-MS is an excellent technique for detection, differentiation, and quantification of BoNT in complex matrices.

Snake-like robots can perform various types of locomotion in the complex environments. In this article, a novel two-layered central pattern generator-based controller is proposed for controlling snake-like robots. To adapt to rough terrain, snake-like robots can dynamically adjust their locomotion through modulating the control parameters of the central pattern generator-based controller based on the sensory feedback. When the parameters are modulated through the step function, the outputs of the central pattern generator-based controller may be unsmooth or discontinuous during the transition process. This will result in stiff and flexible impulses on the motors and gearboxes. In this article, the curvilinear continuity is used to evaluate the continuity degree of the outputs of the central pattern generator-based controller. In order to avoid the damage to the joint motors, two sigmoid transition approaches are proposed. First, a sigmoid parametric modulation method for the central pattern generator-based controller is proposed to eliminate the abrupt changes in the control signals of the joint motors. Second, a sigmoid start-up method is presented to improve the motion efficiency of the snake-like robot. The simulation results of the snake-like robot show that the outputs of the central pattern generator-based controller transit smoothly with the proposed sigmoid parametric modulation method. The snake-like robot can perform a soft start when the sigmoid start-up method is applied. The results demonstrate that the central pattern generator-based controller and the two proposed sigmoid transition approaches are effective.

Red coleoptiles can help crops to cope with adversity and the key genes that are responsible for this trait have previously been isolated from Triticum aestivum, Triticum urartu, and Aegilops tauschii. This report describes the use of transcriptome analysis to determine the candidate gene that controls the trait for white coleoptiles in T. monococcum by screening three cultivars with white coleoptiles and two with red coleoptiles. Fifteen structural genes and two transcription factors that are involved in anthocyanin biosynthesis were identified from the assembled UniGene database through BLAST analysis and their transcript levels were then compared in white and red coleoptiles. The majority of the structural genes reflected lower transcript levels in the white than in the red coleoptiles, which implied that transcription factors related to anthocyanin biosynthesis could be candidate genes. The transcript levels of MYC transcription factor TmMYC-A1 were not significantly different between the white and red coleoptiles and all of the TmMYC-A1s contained complete functional domains. The deduced amino acid sequence of the MYB transcription factor TmMYB-A1 in red coleoptiles was homologous to TuMYB-A1, TaMYB-A1, TaMYB-B1, and TaMYB-D1, which control coleoptile color in corresponding species and contained the complete R2R3 MYB domain and the transactivation domain. TmMYB-a1 lost its two functional domains in white coleoptiles due to a single nucleotide deletion that caused premature termination at 13 bp after the initiation codon. Therefore, TmMYB-A1 is likely to be the candidate gene for the control of the red coleoptile trait, and its loss-of-function mutation leads to the white phenotype in T. monococcum.

In this study, we prepared cubic-phase oleic-acid-coated KMnF3: Yb3+,Er3+ nanoparticles (NPs) and NaYF4:Yb3+,Er3+ NPs, which were about 23 nm. From the down-shifting emissions spectra of the two NPs obtained by 980 nm excitation, we observed the fact that the KMnF3: 18%Yb3+,1%Er3+ NPs were a luminescent material with a broadband near-infrared emission of 1.5 μm, and full-width at half-maximum (FWHM) of 55 cm−1, which was wider than that of the NaYF4: 18%Yb3+,1% NPs. Therefore, we believe that the oleic-acid-coated KMnF3:Yb3+,Er3+ NPs have great potential in fabricating broadband waveguide amplifiers. Through epitaxial growth of a KMnF3: Yb3+ active-shell on the core NPs, we compounded KMnF3:Yb3+,Er3+@KMnF3:Yb3+ core-active-shell NPs whose 1.5-μm infrared emissions intensity was 3.4 times as strong as that of the core NPs. In addition, we manufactured waveguide amplifiers using KMnF3:18%Yb3+,1%Er3+@KMnF3:2%Yb3+ NPs as the core materials of the waveguide amplifiers. When the input signal power was 0.2 mW and the pump power was 200 mW, we achieved a relative gain of 0.6 dB at 1534 nm in a 10-mm long waveguide.

A facile and effective technique to tune the electronic properties of graphene is essential to facilitate the flexibility of graphene-based device performances. Here, the use of hydrazine as a solution-processable and effective n-type dopant for graphene is described. By dropping hydrazine solutions at different concentrations on a graphene surface, the Dirac point of graphene can be remarkably tuned. The transport behavior of graphene can be changed from p-type to n-type accordingly, demonstrating the controllable and adjustable doping effect of the hydrazine solutions. Accompanying the Dirac point shift is an enhanced hysteretic behavior of the graphene conductance, indicating an increasing trap state density induced by the hydrazine adsorbates. The electron-doping of graphene by the hydrazine solutions can be additionally confirmed with graphene/ p-type silicon heterojunctions. The decrease of the junction current after the hydrazine treatment demonstrates an increase of the junction barrier between graphene and silicon, which is essentially due to the electron-doping of graphene and the resultant upshift of the Fermi level. Finally, partially doped graphene is realized and its electrical property is studied to demonstrate the potential of the hydrazine solutions to selectively electron-doping graphene for future electronic applications. [ABSTRACT FROM AUTHOR]

(Pro)renin receptor (PRR) contributes to regulating many physiological and pathological processes; however, the role of PRR-mediated signaling pathways in myocardial ischemia/reperfusion injury (IRI) remains unclear. In this study, we used an in vitro model of hypoxia/reoxygenation (H/R) to mimic IRI and carried out PRR knockdown by siRNA and PRR overexpression using cDNA in H9c2 cells. Cell proliferation activity was examined by MTT and Cell Counting Kit-8 (CCK-8) assays. Apoptosis-related factors, autophagy markers and ß-catenin pathway activity were assessed by real-time PCR and western blotting. After 24 h of hypoxia followed by 2 h of reoxygenation, the expression levels of PRR, LC3B-I/II, Beclin1, cleaved caspase-3, cleaved caspase-9 and Bax were upregulated, suggesting that apoptosis and autophagy were increased in H9c2 cells. Contrary to the effects of PRR downregulation, the overexpression of PRR inhibited proliferation, induced apoptosis, increased the expression of pro-apoptotic factors and autophagy markers, and promoted activation of the β-catenin pathway. Furthermore, all these effects were reversed by treatment with the β-catenin antagonist DKK-1. Thus, we concluded that PRR activation can trigger H/R-induced apoptosis and autophagy in H9c2 cells through the β-catenin signaling pathway, which may provide new therapeutic targets for the prevention and treatment of myocardial IRI. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is one of the most important renal complications associated with diabetes, and the mechanisms are yet to be fully understood. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin-D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The aim of the present study was to explore the potential mechanism by which 1,25(OH)2D3 reduced oxidative stress in diabetic rat kidneys. In this study, we established a vitamin D-deficient spontaneous diabetes model: 5–6 wk of age Zucker diabetic fatty (ZDF) rats were treated with or without 1,25(OH)2D3 for 7 wk, age-matched Zucker lean rats served as control. Results showed that ZDF rats treated with 1,25(OH)2D3 had decreased body mass, food intake, water intake, and urine volume. 1,25(OH)2D3 ameliorated urine glucose, blood glucose and abnormal glucose tolerance. Additionally, 1,25(OH)2D3 significantly lowered microalbuminuria, decreased the glomerular basement membrane thickness, and in some degree inhibited glomerular hypertrophy, mesangial expansion, and tubular dilatation. Furthermore, 1,25(OH)2D3 attenuated renal oxidative damage, as reflected by the levels of malondialdehyde, reduced glutathione, 4-hydroxynonenal, 8-hydroxy-2'-deoxyguanosine, and reactive oxygen species production, and notably inhibited poly(ADP-ribose) polymerase-1 (PARP1), activated sirtuin 1 (SIRT1), and decreased the expression of NADPH oxidase 4 (NOX4). Of interest, the abovementioned proteins could be involved in the antioxidant mechanism of 1,25(OH)2D3 in diabetic rat kidneys. Our study showed that oxidative stress might be a major contributor to DN pathogenesis and uncovered the antioxidant role of 1,25(OH)2D3 in diabetic nephropathy that was associated with the PARP1/SIRT1/ NOX4 pathway. [ABSTRACT FROM AUTHOR]

The transcription factor ATF-2 basic leucine zipper domain (b-ZIP) interaction with the p300 acetyltransferase (HAT) domain is examined and it is shown that p300 HAT autoacetylation can increase the binding affinity. The results have indicated multiple roles for protein acetylation in the regulation of transcription by the p300/CBP and ATF-2.

The distributed alternating direction method of multipliers (ADMM) algorithm is one of the effective methods to solve the global consensus optimization problem. Considering the differences between the communication of intra-nodes and inter-nodes in multicore cluster, we propose a group-based asynchronous distributed ADMM (GAD-ADMM) algorithm: based on the traditional star topology network, the grouping layer is added. The workers are grouped according to the process allocation in nodes and model similarity of datasets, and the group local variables are used to replace the local variables to compute the global variable. The algorithm improves the communication efficiency of the system by reducing communication between nodes and accelerates the convergence speed by relaxing the global consistency constraint. Finally, the algorithm is used to solve the logistic regression problem in a multicore cluster. The experiments on the Ziqiang 4000 showed that the GAD-ADMM reduces the system time cost by 35% compared with the AD-ADMM. [ABSTRACT FROM AUTHOR]

Li(Ni0.8Co0.15Al0.05)O2 (NCA) cathode material for lithium ion batteries is synthesized by calcining Ni- Co-Al hydroxide or carbonate hydroxide hydrate precursor, which is obtained by hydrothermal method, and the NCA cathode material is hierarchical hollow microspheres with the diameter in the range of 3-5 μm and composed of nanoflakes and/or nanowires. The effect of hydrothermal reaction time on the morphologies and the crystalline quality of the NCA cathode material is investigated on the basis of scanning electron microscopy, X-ray diffraction, and tunneling electron microscopy. The NCA cathode material shows smooth and monotonous charge/discharge characteristics, delivers a reversible capacity as 144.4 mAh/g and retains 90.4% after 50 cycles at a current density of 0.1 C between 2.5 and 4.3 V. [ABSTRACT FROM AUTHOR]

Ricin is a highly toxic protein which causes cell death by blocking protein synthesis and is considered a potential bioterrorism agent. Rapid and sensitive detection of ricin toxin in various types of sample matrices is needed as an emergency requirement for public health and antibioterrorism response. An in vitro MALDI TOF MS-based activity assay that detects ricin mediated depurination of synthetic substrates was improved through optimization of the substrate, reaction conditions, and sample preparation. In this method, the ricin is captured by a specific polycolonal antibody followed by hydrolysis reaction. The ricin activity is determined by detecting the unique cleavage product of synthetic oligomer substrates. The detection of a depurinated substrate was enhanced by using a more efficient RNA substrate and optimizing buffer components, pH, and reaction temperature. In addition, the factors involved in mass spectrometry analysis, such as MALDI matrix, plate, and sample preparation, were also investigated to improve the ionization of the depurinated product and assay reproducibility. With optimized parameters, the limit of detection of 0.2 ng/mL of ricin spiked in buffer and milk was accomplished, representing more than 2 orders of magnitude enhancement in assay sensitivity. Improving assay's ruggeddness or reproducibility also made it possible to quantitatively detect active ricin with 3 orders of magnitude dynamic range. [ABSTRACT FROM AUTHOR]

In this publication, we report on the development of a 1400 y = 0.002i x + 0.0356 quantitative enzymatic method for the detection of four botulinum R2 = 0.9903 neurotoxin (BoNT) serotypes responsible for human botulism by MALDI-TOF mass spectrometry. Factors that might affect the linearity and dynamic range for detection of BoNT cleavage products were initially examined, including the amount of peptide substrate and internal standard, the timing of cleavage reaction, and the components in the reaction solution. It was found that a long incubation time produced sensitive results, but was not capable of determining higher toxin concentrations, whereas a short incubation time was less sensitive so that lower toxin concentrations were not detected. In order to overcome these limitations, a two-stage analysis strategy was applied. The first stage analysis involved a short incubation period (e.g., 30 min). If no toxin was detected at this stage, the cleavage reaction was allowed to continue and the samples were analyzed at a second time point (4 h), so that toxin levels lower than 1 mouse LD50 or 55 attomoles per milliliter (55 amol/mL) could be quantified. By combining the results from two-stage quantification, 4 or 5 orders of magnitude in dynamic range were achieved for the detection of the serotypes of BoNT/A, BoNT/B, BoNT/E, or BoNT/F. The effect of multiplexing the assay by mixing substrates for different BoNT serotypes into a single reaction was also investigated in order to reduce the numbers of the cleavage reactions and save valuable clinical samples. [ABSTRACT FROM AUTHOR]

The stability of varicella-zoster virus (VZV) open reading frame (ORF) 63 was analyzed by sequential passage of a virus strain in cell culture. VZV was propagated in culture for 1,206 passages. ORF63 from six passages (18, 220, 516, 730, 1060, and 1,206) was selected and sequenced. Among the six passages, only passage 1,206 showed point mutations at three locations: 551, 618 and 661. In addition, western blot analysis with anti-ORF63 monoclonal antibodies showed no discernable difference in the size of the ORF63 gene product from passage 18 and that from passage 1,206. These results indicate the stability of VZV ORF63 gene in culture over 1,206 passages. [ABSTRACT FROM AUTHOR]

Despite the completion of the Treponema pallidum genome project, only minor genetic differences have been found between the subspecies that cause venereal syphilis (ssp. pallidum) and the nonvenereal diseases yaws (ssp. pertenue) and bejel (ssp. endemicum). In this paper, we describe sequence variation in the arp gene which allows straightforward differentiation of ssp. pallidum from the nonvenereal subspecies. We also present evidence that this region is subject to positive selection in ssp. pallidum, consistent with pressure from the immune system. Finally, the presence of multiple, but distinct, repeat motifs in both ssp. pallidum and Treponema paraluiscuniculi (the pathogen responsible for rabbit syphilis) suggests that a diverse repertoire of repeat motifs is associated with sexual transmission. This study suggests that variations in the number and sequence of repeat motifs in the arp gene have clinical, epidemiological, and evolutionary significance. [ABSTRACT FROM AUTHOR]

We report here the application of electrospray ionization tandem mass spectrometry for the characterization of protein ubiquitylation, an important posttranslational modification of cellular proteins. Trypsin digestion of ubiquitin-conjugated proteins produces diglycine branched peptides containing the modification sites. Chemical derivatization by N-terminal sulfonation was carried out on several model peptides for the formation of a characteristic fragmentation pattern in their MS/MS analysis. The fragmentation of derivatized singly charged peptides results in a product ion distribution similar to that already observed by MALDI-TOF MS/MS. Signature fragments distinguished the diglycine branched peptides from other modified and unmodified peptides, while the sequencing product ions reveal the amino acid sequence and the location of the ubiquitylation site. Doubly charged peptide derivatives fragment in a somewhat different manner, but several fragments characteristic to diglycine branched peptides were observed under low collision energy conditions. These signature peaks can also be used to identify peptides containing ubiquitylation sites. In addition, a marker ion corresponding to a glycine-modified lysine residue produced by high-energy fragmentation provides useful information for identity verification. The method is demonstrated by the analysis of three ubiquitin-conjugated proteins using LC/MS/MS. [ABSTRACT FROM AUTHOR]

The biological significance of recently described modifiable residues in the globular core of the bovine nucleosome remains elusive. We have mapped these modification sites onto the Saccharomyces cerevisiae histones and used a genetic approach to probe their potential roles both in heterochromatic regions of the genome and in the DNA repair response. By mutating these residues to mimic their modified and unmodified states, we have generated a total of 39 alleles affecting 14 residues in histones H3 and H4. Remarkably, despite the apparent evolutionary pressure to conserve these near-invariant histone amino acid sequences, the vast majority of mutant alleles are viable. However, a subset of these variant proteins elicit an effect on transcriptional silencing both at the ribosomal DNA locus and at telomeres, suggesting that posttranslational modification(s) at these sites regulates formation and/or maintenance of heterochromatin. Furthermore, we provide direct mass spectrometry evidence for the existence of histone H3 K56 acetylation in yeast. We also show that substitutions at histone H4 K91, K59, S47, and R92 and histone H3 K56 and K115 lead to hypersensitivity to DNA-damaging agents, linking the significance of the chemical identity of these modifiable residues to DNA metabolism. Finally, we allude to the possible molecular mechanisms underlying the effects of these modifications. [ABSTRACT FROM AUTHOR]

Investigates the incorporation of five unnatural tyrosine kinase analogs into protein substrate Src using expressed protein litigation. Rates of Csk-catalyzed phosphorylation of tyrosine analogs; Evaluation of semisynthetic substrates; Effects of tyrosine phenol hydroxyl on Src ground state binding affinity for Csk.

Focuses on the molecular recognition of protein substrates by protein tyrosine kinase. Use of purified recombinant Csk and Src proteins in tyrosine phosphorylation; Features of the cell signal transduction; Association of Csk phosphorylation with down-regulation of tyrosine kinase activity.